v-Triazolines. XXXIX . 1,2,4-Triaryl-3-aminopyrroles. Unusual Reaction Products in the Pyrolysis of 5-Amino-v-triazolines and the Crystal Structure of 2-(3-Morpholin-4-yl-2,4-pyrrol-1-yl)benzonitrile

Pyrolysis of 4-aryl-5-amino-v-triazolines affords, generally, amidines and/or benzanilides. Pyrolysis of 4-aryl-5-morpholino-v-triazolines 6 , together with the expected amidines 7 and/or aryanilides 8 , produced the morpholinopyrroles 9 . The reaction mechanism of this unusual transformation is discussed. Influence of solvent dipole moment in pyrrole formation is suggested. Pyrrole 9a [i.e. 2-(3-morpholin-4-yl-2,4-pyrrol-1-yl)-benzonitrile] has been fully characterized and its molecular structure has been determined by X-ray diffraction analysis.     

Oscillatory kinetics and mechanism of the chromate catalyzed decomposition of hydrogen peroxide

Oscillatory change of pH occurs during the chromate-catalyzed decomposition of hydrogen peroxide in a weakly acidic medium at elevated temperature and at high initial concentration of hydrogen peroxide. In a closed system, there are only two or three periods, but sustained oscillation occurs in a CSTR. In a CSTR bistability is also found. In closed systems the temperature exhibits a great maximum (up to 15°C increase), in a CSTR sustained oscillation occurs at a constant stationary temperature.     

Shape recognition of alkylammonium ions by 1,3-bridged calix[5]arene crown-6 ethers: endo- vs exo-cavity complexation

A series of tri-O-substituted 1,3-bridged calix[5]arene crown-6 ethers bearing alkyl, arylalkyl, alkoxyalkyl, and alkoxycarbonylmethyl residues at the lower rim and either (t)()Bu or H substituents at the upper rim have been synthesized. (1)H NMR studies have shown that p-tert-butylcalix[5]crowns, irrespective of the size and nature of their lower rim pendant groups, adopt preorganized conelike conformations, whereas p-H-calix[5]crowns with bulky substituents preferentially exist in solution as partial cone conformers (C(1) symmetry). Calix[5]crown derivatives behave as mono- or ditopic receptors for isomeric butylammonium ions, forming endo-cavity (inside the calixarene cup) and/or exo-cavity (at the crown ether moiety) 1:1 complexes according to the shape of the guest. These two binding modes can be clearly distinguished and monitored by (1)H NMR titration experiments.     

Models of pesticides inside cavities of molecular dimensions. A role of the guest inclusion in the dechlorination process

The reduction mechanism of the pesticide vinclozoline (3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-2,4-dione) was studied in nonaqueous solvents in the confined environment of a cyclodextrin (CD) cavity. The effect of the cavity dimensions on the mechanism of the redox process was evaluated using glucose as a reference and using three cyclodextrin molecules of different cavity sizes, namely, alphaCD, betaCD, and gammaCD. In the absence of CD the main reduction product of vinclozoline in the first reduction step is dichloroaniline. An addition of glucose leads to a quantitative change of mechanism with 10 products in total. Addition of CD, however, leads exclusively to dechlorination of the phenyl ring. The degree of dechlorination depends strongly on the choice of cyclodextrin molecule. The importance of the complex formation equilibria in the change of the mechanism is supported by a series of semiempirical AM1 quantum-mechanical calculations. Very good correlation (correlation coefficient 0.995) was obtained between the complex stabilization energy of the inclusion complex and the degree of pesticide dechlorination. Additionally, we were able to show that the complexes are stabilized by the formation of intermolecular hydrogen bonds between the host and guest species. CD molecules do not simply act as proton donors in a nonaqueous environment, but also protect parts of the molecule included within the cavity and steer the degradation process toward fewer products.     

Effect of the addition of a nonionic surfactant on the complex poly(asparagine)--cationic surfactant

Poly(asparagine) (pAsn) at 0.1wt % in the presence of dodecyltrimethylammonium bromide (DTAB) and pentaoxyethylene octyl ether (C(8)E(5)) at 1:1 molar ratio leads to the formation of mixed DTAB/C(8)E(5) micelle-like aggregates onto the polypeptide as a total surfactant critical association concentration (cac) is reached, as revealed by surface tension measurements and NMR chemical shifts. Two-dimensional nuclear Overhauser enhancement spectroscopy (NOESY) capable of revealing spatial relationships among proximal protons has been performed on the pAsn-DTAB-C(8)E(5)-water system to study structural details of the surfactant-polypeptide aggregates. NOESY cross-peaks at sample temperature of 298.15 K indicate that the polypeptide interacts with the DTAB/C(8)E(5) micelle-like aggregates. The NOE intermolecular effects also show direct interactions between surfactant and polypeptide in the pAsn-DTAB-water system, whereas no interaction has been revealed in the pAsn-C(8)E(5)-water system. Furthermore, the experimental evidence suggest that the DTAB-polypeptide complex is mainly driven by the polar attraction between the two molecules.     

X-ray structure and circular dichroism of pure rotamers of bis[guanosine-5'-monophosphate(-1)](N,N,N',N'-tetramethylcyclohexyl-1,2-diamine)platinum(II) complexes that have R,R and S,S configurations at the asymmetric diamine

The use of a sterically hindered diamine ligand (Me(4)DACH) has allowed for the first time, the isolation and characterization, both in the solid state (X-ray crystallography) and in solution (circular dichroism), of pure DeltaHT rotamers of [Pt(Me(4)dach)(5'-GMP)(2)] (compounds 1 and 2 for R,R and S,S configurations of the Me(4)DACH ligand, respectively). Comparison of the CD spectra obtained for each rotamer, which differ only in the chirality of the Me(4)DACH ligand (R,R or S,S) or in the chirality of the HT conformation (Delta or Lambda), allowed us to conclude that, in the 200-350 nm range, the contributions to the overall CD spectrum that stem from diamine chirality and diamine-induced chirality of platinum d--d transitions or from sugar chirality are negligible relative to the exciton chiral coupling that occurs for pi-pi* transitions of the cis guanines. Accurate molecular structures of 1.10 D(2)O and 2.14 D(2)O (conventional crystallographic agreement indexes R(1) convergent to 2.07 % and 2.18 %, respectively) revealed that the crystallized rotamers have a DeltaHT conformation that is in agreement with all previously reported X-ray structures of [Pt(diamine)(nucleos(t)ide)(2)] complexes. This conformation allows the 5'-phosphate to be located in proximity to the Me(4)DACH ligand so that (P)O...HC(N) hydrogen-bond interactions exists in both complexes. For both structures, the canting of the guanine planes on the coordination plane is right-handed (R; canting angle (Phi) of 80.9 degrees and 73.2 degrees, respectively); this indicates that the canting direction is driven by the HT conformation chirality (Delta for both compounds) and not by the chirality of the carrier ligand (different for the two compounds). Density functional theory analysis of the conformational space as a function of Phi indicated a good agreement between the computed and experimental structures. The increase in energy for Phi values below 65 degrees and 55 degrees (for 1 and 2, respectively) is mainly due to the short intramolecular contacts between C(8)H and the cis N-Me groups on the same side of the platinum coordination plane.     

Zum Mechanismus der nucleophilen Addition an 2,3-Dihydrodipyrrin-1(10H)-one

¹H NMR-spectroscopic investigations of the acid catalyzed addition of methanol to dihydrodipyrrinones (Z)-2, (E)-2, and4 show the C-protonation of their enamide parts to be the first and rate determining step forming the key intermediate, the N-acyl-immonium ion N⁺. Its ability to add nucleophiles diastereoselectively can be used to prepare the adductsl-3 andl-5. Exclusive formation of thelike-isomer can be explained by a stereoelectronically favoured approach of the nucleophile and by the thermodynamically favoured arrangement of the bulky ring substituents. Both explanations are based on low temperature X-ray crystal structure determinations: in the first place, the orientation of the added nucleophile could be found to be nearly parallel to the -plane of the lactam unit and quasi-axial with respect to theenvelope-like conformation of the five-ring lactam; in the second place, the relative orientation of the methoxycarbonyl-metyl-group at C-3 and the pyrrolylmethyl-substituent at C-4 could be found to be atrans-quasi-diequatorial one.

     

The effects of cationic and zwitterionic micelles on the keto-enol interconversion of 2-phenylacetylfuran and 2-phenylacetylthiophene

The presence of micelles from cationic and zwitterionic surfactants increases the apparent acidity of either the keto and the enol forms of 2-phenylacetylfuran (2PAF) and 2-phenylacetylthiophene (2PAT). This effect can be attributed to the affinity of the surfactant micelles for the enolate of the two substrates. Although the equilibrium constants for keto-enol tautomerism of 2PAF and 2PAT, K_T=[enol]/[ketone]=pK_a^KH−pK_a^EH, do not change much, the presence of micelles provides an efficient method for producing appreciable quantities of the enolates under mild experimental conditions and in aqueous solutions. The obtained rate-profiles for the ketonisation reactions and the consistency of the kinetic rate constants over a wide range of ‘pH’ in several overlapping buffers indicate that the pH of the aqueous pseudophase (but not that at the micellar surface) can be controlled by buffers. Moreover, the increase of the acidity and the decrease of the ‘water’ rate of ketonisation of the enols of 2PAF and 2PAT upon addition of surfactants allow the uncovery of a metal ion catalysed pathway that cannot be observed in absence of surfactants.     

Synthesis, structure and conformation of partially-modified retro- and retro-inverso psi[NHCH(CF3)]Gly peptides

Partially modified retro- (PMR) and retro-inverso (PMRI) psi[NHCH(CF(3))]Gly peptides, a conceptually new class of peptidomimetics, have been synthesized in wide structural diversity and variable length by aza-Michael reaction of enantiomerically pure alpha-amino esters and peptides with enantiomerically and geometrically pure N-4,4,4-trifluorocrotonoyl-oxazolidin-2-ones. The factors underlying the observed moderate to good diastereocontrol have been investigated. The conformations of model PMR-psi[NHCH(CF(3))]Gly tripeptides have been studied in solution by (1)H NMR spectroscopy supported by MD calculations, as well as in the solid-state by X-ray diffraction. Remarkable stability of turn-like conformations, comparable to that of parent malonyl-based retropeptides, was evidenced, as a likely consequence of two main factors: 1) severe torsional restrictions about sp(3) bonds in the [CO-CH(2)-CH(CF(3))-NH-CH(R)-CO] module, which is biased by the stereoelectronically demanding CF(3) group and the R side chain; 2) formation of nine-membered intramolecularly hydrogen-bonded rings, which have been clearly detected both in CHCl(3) solution and in some crystal structures. The former factor seems to be more important, as turn-like conformations were found in the solid-state even in the absence of intramolecular hydrogen bonding. The relative configuration of the -C*H(CF(3))NHC*H(R)- stereogenic centers has a major effect on the stability of the turn-like conformation, which seems to require a syn stereochemistry. X-ray diffraction and ab initio computational studies showed that the [-CH(CF(3))NH-] group can be seen as a sort of hybrid between a peptide bond mimic and a proteolytic transition state analogue, as it combines some of the properties of a peptidyl -CONH- group (low NH basicity, CH(CF(3))-NH-CH backbone angle close to 120 degrees, C-CF(3) bond substantially isopolar with the C=O) with some others of the tetrahedral intermediate [-C(OX)(O(-))NH-] involved in the protease-mediated hydrolysis reaction of a peptide bond (high electron density on the CF(3) group, tetrahedral backbone carbon).